The majority of our knowledge about the molecular mechanisms of cellular responses to ionizing radiation is based on experiments with traditional cell culture models. For models, cancer cell lines were used the most often, which historically was reasonable given that radiation therapy of cancers is an important clinical application of ionizing radiation in medicine. Now, concerns are being expressed about the consequences of lower exposures, i.e. diagnostic imaging test exposures. It is quite obvious that hESC, primary cell lines, established normal cell lines and cancer cell lines have different responses to IR. The results obtained from experiments using cultures of terminally differentiated cells may not reflect the response to IR of a normal tissue that consists of multiple cell types, including progenitor and tissue stem cells. Because we have access to a number of hESC lines approved for NIH Intramural experiments, I wish to use these genetically distinct hESC to determine by experimentation whether patterns of gene activation following irradiation are truly common across all early human cell lines or whether each line will exhibit, in part because of genetic differences, a distinct response to external and internal irradiations of various types and levels.